Watson S A, Morris T M, Robinson G, Crimmin M J, Brown P D, Hardcastle J D
Department of Surgery, Queen's Medical Centre, University Hospital, Nottingham, United Kingdom.
Cancer Res. 1995 Aug 15;55(16):3629-33.
The effect of the matrix metalloproteinase inhibitor batimastat was evaluated in two human colorectal cancer metastasis models involving: (a) the liver-invasive tumor C170HM2 and (b) the lung-invasive tumor AP5LV, both of which have been shown to express the M(r) 72,000 type IV collagenase. Batimastat at concentrations between 0.01 and 3.0 micrograms/ml had no direct cytotoxic effects on the in vitro growth of the cell lines. In the liver-invasive tumor model, batimastat administered i.p. from day 10 to termination of the therapy (day 39) at 40 mg/kg reduced both the mean number of liver tumors (35% of vehicle-treated control; P < 0.05) and the cross-sectional area of the tumors (43% of vehicle-treated control; P < 0.05). In the lung-invasive tumor model, batimastat administered daily (40 mg/kg i.p.) significantly reduced tumor weight within the lung (72% of vehicle-treated control; P < 0.05) but did not significantly affect nodule number. In the latter model, in which the take rate was unaffected, tumor cells were introduced into the lateral tail vein, and lung localization may have been a physical phenomenon not involving invasion. In the former model, tumor cells were introduced directly into the peritoneal cavity, and from there the cells adhered to and invaded the liver capsule. Because the take rate is significantly reduced, it may be that the matrix metalloproteinases are involved in this process. Batimastat may be a therapeutic modality for the treatment of colorectal cancer metastasis.
在两种人类结直肠癌转移模型中评估了基质金属蛋白酶抑制剂batimastat的效果，这两种模型涉及：（a）肝侵袭性肿瘤C170HM2和（b）肺侵袭性肿瘤AP5LV，这两种肿瘤均已显示表达分子量为72,000的IV型胶原酶。浓度在0.01至3.0微克/毫升之间的batimastat对细胞系的体外生长没有直接细胞毒性作用。在肝侵袭性肿瘤模型中，从第10天至治疗结束（第39天）腹腔注射40毫克/千克的batimastat可减少肝肿瘤的平均数量（为溶媒处理对照组的35%；P<0.05）以及肿瘤的横截面积（为溶媒处理对照组的43%；P<0.05）。在肺侵袭性肿瘤模型中，每日腹腔注射（40毫克/千克）batimastat可显著降低肺内肿瘤重量（为溶媒处理对照组的72%；P<0.05），但对结节数量没有显著影响。在后者模型中，接种率未受影响，肿瘤细胞被引入外侧尾静脉，肺定位可能是一种不涉及侵袭的物理现象。在前者模型中，肿瘤细胞被直接引入腹腔，细胞从那里黏附并侵袭肝包膜。由于接种率显著降低，可能是基质金属蛋白酶参与了这一过程。Batimastat可能是一种治疗结直肠癌转移的治疗方式。
